A5025526658- Metabolomics and Mass Spectrometry Studies
- Cancer, Lipids, and Metabolism
- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- Cancer, Hypoxia, and Metabolism
- Advanced Proteomics Techniques and Applications
- Aquaculture disease management and microbiota
- Lipid metabolism and biosynthesis
- Retinoids in leukemia and cellular processes
- Isotope Analysis in Ecology
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- CAR-T cell therapy research
- Anesthesia and Neurotoxicity Research
- Cardiac Arrest and Resuscitation
- Molecular Biology Techniques and Applications
- Histone Deacetylase Inhibitors Research
- Diet and metabolism studies
- Vitamin C and Antioxidants Research
- Peroxisome Proliferator-Activated Receptors
- Cardiac Ischemia and Reperfusion
- Antifungal resistance and susceptibility
- Aquaculture Nutrition and Growth
- Environmental Toxicology and Ecotoxicology
- Advanced Chemical Sensor Technologies
University of Birmingham
2015-2025
University of Cambridge
2023
Centre for Environment, Fisheries and Aquaculture Science
2008
Newcastle University
2000
Direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry (DI nESI FT-ICR MS) offers high accuracy and resolution for analyzing complex metabolite mixtures. High dynamic range across a wide range, however, can only be achieved at the expense of accuracy, since large numbers ions entering ICR detector induce adverse space-charge effects. Here we report an optimized strategy wide-scan DI MS that increases but maintains accuracy. It comprises collection...
Cellular metabolism is altered during cancer initiation and progression, which allows cells to increase anabolic synthesis, avoid apoptosis adapt low nutrient oxygen availability. The metabolic nature of enables patient status be monitored by metabolomics lipidomics. Additionally, monitoring patients or biological models can used greater understand the action anticancer therapeutics. Discuss how lipidomics (i) identify biomarkers (ii) mechanism-of-action therapies. considerations that...
A challenge facing metabolomics in the analysis of large human cohorts is cross-laboratory comparability quantitative measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with Biocrates AbsoluteIDQ p400HR kit, to quantify up 408 metabolites. The included plasma and serum from male female donors, mouse rat plasma, as well NIST SRM 1950 reference plasma. metabolite classes covered range polar (e.g., amino acids biogenic...
Abstract Introduction The use of large, non-sample specific metabolite reference libraries often results in high proportions false positive annotations untargeted metabolomics. Objective This study aimed to measure and curate a library polar metabolites lipids present cardiac microtissues. Results Untargeted ultra-high performance liquid chromatography-coupled mass spectrometry measurements microtissue intracellular extracts were annotated by comparison against four spectral databases...
Currently there is limited information available on the accuracy and precision of relative isotopic abundance (RIA) measurements using high-resolution direct-infusion mass spectrometry (HR DIMS), it unclear if this can benefit automated peak annotation in metabolomics. Here we characterize RIA Thermo LTQ FT Ultra (resolution 100,000-750,000) Orbitrap (R = 100,000) spectrometers. This first involved reoptimizing SIM-stitching method (Southam, A. D. Anal. Chem. 2007, 79, 4595-4602) for Ultra,...
Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic non-transformed but surprisingly not cells. Molecules underlying this adaptation may provide alternative drug targets. Here, we demonstrate that diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral triacylglyceride...
While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due weak category justifications based on structural similarity only. Metabolomics provides a route robust categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, best-practice guidance required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising...
Direct-infusion electrospray-ionization Fourier transform ion cyclotron resonance mass spectrometry (DI ESI FT-ICR MS) is increasingly being utilized in metabolomics, including the high sensitivity selected monitoring (SIM)-stitching approach. Accurate signal quantification and discrimination of real signals from noise remain major challenges for this approach, with both adversely affected by factors suppression during electrospray, ion-ion interactions detector cell, thermally-induced white...
The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, categorized as a "red list" pollutant, being particularly hazardous aquatic life. It acts primarily cholinesterase inhibitor, but evidence suggests it can also act androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity well-established, information regarding target off-target molecular toxicities limited. Here...
Abstract The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity acute myelogenous leukemia (AML) endemic Burkitt lymphoma (eBL) patients; however, its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis a hallmark many cancers these drugs can affect lipid metabolism, we hypothesized BaP exerts effects by disrupting lipogenesis. We applied mass spectrometry–based lipidomics gene protein...
In this study we assess multiple sample preparation methods for UHPLC-MS metabolic phenotyping analysis of human urine and plasma. All are discussed in terms metabolite lipid coverage reproducibility.
Abstract Untargeted metabolomics is an established approach in toxicology for characterising endogenous metabolic responses to xenobiotic exposure. Detecting the and its biotransformation products as part of analysis provides opportunity simultaneously gain deep insights into fate metabolism, associate internal relative dose directly with responses. This integration untargeted exposure response measurements a single assay has yet be fully demonstrated. Here we assemble workflow discover...
Histopathologically well-characterized fish liver was analyzed by 800 MHz 1H NMR metabolomics to identify metabolic changes between healthy and tumor tissue. Data were multivariate statistics correlation networks, results revealed elevated anaerobic metabolism reduced choline in Significant negative correlations observed alanine-acetate (p = 3.0 × 10−5) proline-acetate 0.003) tumors only, suggesting alanine proline are utilized as alternative energy sources flatfish tumors.
In the fight against antibiotic resistance, drugs that target resistance mechanisms in bacteria can be used to restore therapeutic effectiveness of antibiotics. The multidrug efflux complex AcrAB-TolC is most clinically relevant pump Enterobacterales and a for drug discovery. Inhibition protein AcrB allows intracellular accumulation wide variety antibiotics, effectively restoring their potency. To facilitate development inhibitors, it desirable discover native substrates pump, as these could...
<title>Abstract</title> Background Ruminants produce methane (CH<sub>4</sub>) via ruminal methanogenic archaea during microbial fermentation. Condensed tannins (CTs) can mitigate CH<sub>4</sub> production by inhibiting methanogens or reducing H<sub>2</sub> in the rumen through decreased fibre digestion. Additionally, CTs bind to proteins rumen, protecting them from degradation resulting ammoniacal N and enhanced nitrogen uptake hindgut. This pioneering research is first explore potential of...
Environmental metabolomics is increasingly used to investigate organismal responses complex chemical mixtures, including waste water effluent (WWE). In parallel, sensitive analytical methods are being in studies, particularly mass spectrometry. This introduces a considerable, yet overlooked, challenge that high sensitivity will not only improve the detection of endogenous metabolites biological specimens but also exogenous chemicals. If these often unknown xenobiotic features removed from...
Abstract Acute myeloid leukaemia (AML) is a life threatening cancer for which there an urgent clinical need novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro vivo . Elucidation the BaP mechanism action required order to understand how maximise benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) Raman...
Metabolic phenotyping of tissues uses metabolomics and lipidomics to measure the relative polar nonpolar (lipid) metabolite levels in biological samples. This approach aims understand disease biochemistry identify biochemical markers disease. Sample preparation methods must be reproducible, sensitive (high lipid yield), ideally rapid. We evaluated three biphasic for compound extraction (chloroform/methanol/water, dichloromethane/methanol/water, methyl tert-butyl ether [MTBE]/methanol/water),...
Interactions between epigenome and the environment in biology disease are of fundamental importance. The incidence hepatocellular adenomas flatfish exceeds 20% some environments forming a unique opportunity to study environmental tumorigenesis general relevance cancer humans. We report novel finding marked DNA methylation metabolite concentration changes histopathologically normal tissue distal tumors fish liver. A multi-"omics" discovery approach led targeted quantitative gene transcription...
Idiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised pressure. Weight loss leads to the reduction Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and The potential mechanisms which weight pressure are unknown were focus of this study. Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 120 min following standardized meal) conducted pre-...